The aim of this project is to study the neurophysiological effects of psychotomimetic (psychotogenic, hallucinogenic) drugs on chemically-identified brain neurons. The research plan focusses on monoaminergic neurons (e.g., serotonergic and noradrenergic) as they are known to contain endogenous transmitter substances chemically related to psychotomimetic drugs. Two major classes of psychotomimetic drugs are to be investigated in rats by single-cell recording techniques: (1) the psychedelics (e.g., LSD and mescaline) and (2) the amphetamines. The specific research proposals are as follows: 1. Continuation of studies on the inhibition of 5-HT neurons by indoleamine hallucinogens and the hypothesized disinhibition of postsynaptic neurons. 2. Initiation of intracellular recordings to investigate autoreceptor-mediated collateral inhibition in the raphe and to analyze the ionic mechanisms through which indoleamine hallucinogens inhibit 5-HT neurons. 3. Initiation of studies on the development of tolerance to indoleamine and phenethylamine hallucinogens. 4. Initiation of studies on the facilitatory actions of hallucinogens on sensory pathways (including afferents to the locus coeruleus). 5. Initiation of studies on the mechanisms by which NE and the amphetamine isomers modulate the activity of lateral geniculate neurons. In general, we have found that low doses of the psychotomimetic drugs have two types of actions on neurotransmission: facilitatory and disinhibitory. The above proposals are aimed, in part, at determining which of these synaptic actions are most closely linked to the psychotomimetic actions of these drugs.